Alisol B 23-acetate, a new promoter for cholesterol efflux from dendritic cells, alleviates dyslipidemia and inflammation in advanced atherosclerotic mice.

Atherosclerosis (AS) is characterized by dyslipidemia and chronic inflammation. In the high-fat environment, the lipid metabolism of dendritic cells (DCs) is abnormal, which leads to abnormal immune function, promotes the occurrence of immune inflammatory reactions, and promotes the development of AS. Alisol B 23-acetate (23B) is a triterpenoid in the rhizomes of Alisma, which is a traditional Chinese medicine. Here, we identified cholesterol metabolism-related targets of 23B through a virtual screen, and further transcriptome analysis revealed that 23B can change antigen presentation and cholesterol metabolism pathways in cholesterol-loaded DCs. In vitro experiments confirmed that 23B promoted cholesterol efflux from ApoE DCs, reduced the expression of MHC II, CD80, and CD86, and inhibited the activation of CD4 T cells and the production of inflammatory cytokines IL-12 and IFN-γ. In advanced AS mice, 23B can decrease triacylglycerol (TG) levels and increase high-density lipoprotein-cholesterol (HDL-C) levels in plasma and the expression of cholesterol efflux genes in the aorta. Neither helper T cells 1 (Th1) nor regulatory T cells (Tregs) in peripheral blood changed significantly in the presence of 23B, but 23B reduced the levels of IL-12 and IFN-γ in serum. However, 23B did not change the total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels in serum or lipid accumulation in the aorta. Moreover, 23B did not increase the production of IL-10 and TGF-β1 in vivo or in vitro. These results indicate that 23B promotes cholesterol efflux from DCs, which can improve the immune inflammatory response and contribute to controlling the inflammatory status of AS.